This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00332-07v1 75/7/3455    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, H.-H. Articles by Paoletti, L. C. Search for Related Content PubMed PubMed Citation Articles by Yang, H.-H. Articles by Paoletti, L. C.

 Previous Article  |  Next Article 

Infection and Immunity, July 2007, p. 3455-3461, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.00332-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Recombinant Group B Streptococcus Beta C Protein and a Variant with the Deletion of Its Immunoglobulin A-Binding Site Are Protective Mouse Maternal Vaccines and Effective Carriers in Conjugate Vaccines

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Received 2 March 2007/ Returned for modification 16 April 2007/ Accepted 22 April 2007

Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immunoglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCP^IgA), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCP^IgA). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCP^IgA, III-rBCP, and III-rBCP^IgA opsonized GBS strains A909 (Ia/BCP⁺) and H36B (Ib/BCP⁺) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCP^IgA also opsonized strain M781 (III/BCP^–). Vaccination of female mice with either rBCP or rBCP^IgA protected 40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCP^IgA-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCP^IgA proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCP^IgA could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP.

Published ahead of print on 30 April 2007.

Editor: A. Camilli

This article has been cited by other articles:

• Yang, H.-H., Mascuch, S. J., Madoff, L. C., Paoletti, L. C. (2008). Recombinant Group B Streptococcus Alpha-Like Protein 3 Is an Effective Immunogen and Carrier Protein. CVI 15: 1035-1041 [Abstract] [Full Text]